Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage
Artikel i vetenskaplig tidskrift, 2023

Background: Multiple sclerosis (MS) and presymptomatic axonal injury appear to develop only after an Epstein-Barr virus (EBV) infection. This association remains to be confirmed across a broad preclinical time range, for lytic and latent EBV seroreactivity, and for potential cross-reacting antigens. Methods: We performed a case-control study with 669 individual serum samples obtained before clinical MS onset, identified through cross-linkage with the Swedish MS register. We assayed antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18, glycoprotein 350 (gp350), the potential cross-reacting protein anoctamin 2 (ANO2) and the level of sNfL, a marker of axonal injury. Results: EBNA1 (latency) seroreactivity increased in the pre-MS group, at 15-20 years before clinical MS onset, followed by gp350 (lytic) seroreactivity (p=0.001-0.009), ANO2 seropositivity appeared shortly after EBNA1-seropositivity in 16.7% of pre-MS cases and 10.0% of controls (p=0.001).With an average lag of almost a decade after EBV, sNfL gradually increased, mainly in the increasing subgroup of seropositive pre-MS cases (p=8.10-5 compared with non-MS controls). Seropositive pre-MS cases reached higher sNfL levels than seronegative pre-MS (p=0.038). In the EBNA1-seropositive pre-MS group, ANO2 seropositive cases had 26% higher sNfL level (p=0.0026). Conclusions: Seroreactivity against latent and lytic EBV antigens, and in a subset ANO2, was detectable on average a decade before the appearance of a gradually increasing axonal injury occurring in the last decade before the onset of clinical MS. These findings strengthen the hypothesis of latent EBV involvement in the pathogenesis of MS.

MULTIPLE SCLEROSIS

VIROLOGY

Författare

Daniel Jons

Göteborgs universitet

Viktor Grut

Umeå universitet

Tomas Bergström

Göteborgs universitet

Sahlgrenska universitetssjukhuset

Henrik Zetterberg

Göteborgs universitet

Sahlgrenska universitetssjukhuset

Martin Biström

Umeå universitet

Martin Gunnarsson

Faculty of Medicine and Health

M Vrethem

Linköpings universitet

Nicole Brenner

Deutsches Krebsforschungszentrum (DKFZ)

Julia Butt

Deutsches Krebsforschungszentrum (DKFZ)

Kaj Blennow

Göteborgs universitet

Sahlgrenska universitetssjukhuset

Staffan Nilsson

Göteborgs universitet

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

Ingrid Kockum

Karolinska Institutet

Tomas Olsson

Karolinska Institutet

Tim Waterboer

Deutsches Krebsforschungszentrum (DKFZ)

Peter Sundström

Umeå universitet

Oluf Andersen

Göteborgs universitet

Journal of Neurology, Neurosurgery and Psychiatry

0022-3050 (ISSN) 1468-330X (eISSN)

Vol. 95 331868

Ämneskategorier

Neurovetenskaper

Neurologi

Cancer och onkologi

DOI

10.1136/jnnp-2023-331868

PubMed

37802637

Mer information

Senast uppdaterat

2024-07-17